Implantation of normal myoblasts/fibroblasts (co-culture) into dystrophic solei of histocompatible mice improved the structure and functions of the muscles to almost normal. The present project aims to determine if treating dystrophic hosts with the immunosuppressant clyclosporine (CsA) will permit histoincompatible clones of normal myoblasts to survive and develop in their muscles. Applicability of this new technique of genetic complementation to prevent locomotive and respiratory muscle weakness in hereditary myopathies will be tested in dystrophic mice. Since histocompatible normal myoblasts are not readily available for transplant in humans, this project is vital before clinical trials. Normal myoblasts (G8-1) cloned from SJL mice will be injected into various muscle groups in the right hind limb and the intercostal muscles in the right thorax of 20-day-old normal or dystrophic C57BL/6J mice. Host mice receives subcutaneous injections of CsA daily. Survival and development of donor myoblasts in host muscles will be analyzed with electrophoresis and immunocytochemistry of muscle isozymes of glucose phosphate isomerase (GPI). Donor cells produce GPI-1AA and host cells produce GPI-IBB. Presence of GPI-1AB in electrophoresis will substantiate intracellular mosaicism. So will be the monoclone immunocytochemical demonstration of GPI- 1AA and GPI-1BB within single cells. Different groups of test and control muscles will be compared at 2, 4, and 6 months after injection. Muscle mechanophysiology, cellular resting potential and histology will be examined to determine if test muscles exhibit improved structure and function. Genetic mosaicism quantified each time with GPI electrophoresis and immunocytochemistry will be correlated to phenotype indication by physiology and histology. The minimal ratio of normal/dystrophic genotype mosaicism necessary to produce normal phenotype will be determined at the cellular and at the muscle levels. Musclee development will be compared between the right and the left sides of the hosts. Appropriate control experiments will be conducted. Results from this project will be compared with those obtained from implantation of histocompatible GPI-ICC myoblasts/fibroblasts.